The present invention relates generally to peritoneal dialysis and solutions for the same. More specifically, the present invention relates to the use of modified icodextrins in peritoneal dialysis solutions as an osmotic agent and as an alternative to the use of glucose as an osmotic agent. The present invention also relates to methods of preparing peritoneal dialysis solutions that are stable under autoclaving conditions.
Dialysis provides a method for supplementing or replacing renal function in certain patients. Principally, hemodialysis and peritoneal dialysis are the two methods that are currently utilized.
In hemodialysis, the patient's blood is passed through an artificial kidney dialysis machine. A membrane in the machine acts as an artificial kidney for cleansing the blood. Because it is an extracorporeal treatment that requires special machinery, hemodialysis is fraught with certain inherent disadvantages such as the availability of dialysis machines and the possibility of infection and contamination.
To overcome the disadvantages associated with hemodialysis, peritoneal dialysis was developed. Peritoneal dialysis utilizes the patient's own peritoneum as a semi-permeable membrane. The peritoneum is a membranous lining of the abdominopelvic walls of the body. The peritoneum is capable of acting as a natural semi-permeable membrane because of its large number of blood vessels and capillaries.
In operation, a peritoneal dialysis solution is introduced into the peritoneal cavity utilizing a catheter. After a sufficient period of time, an exchange of solutes between the dialysate and blood is achieved. Fluid removal is achieved by providing a suitable osmotic gradient from the dialysate to the blood to permit water outflow from the blood. This allows the proper acid-base, electrolyte and fluid balance to be achieved in the blood. After an appropriate dwell period, the dialysis solution or dialysate is drained from the body through a catheter.
Conventional peritoneal dialysis solutions contain glucose as an osmotic agent to maintain the osmotic pressure of the solution higher than the physiological osmotic pressure (about 285 mOsmol/kg). Glucose is a preferred osmotic agent because it provides rapid ultrafiltration rates. However, certain disadvantages have become associated with the use of glucose.
For example, glucose is known to decompose to 5-hydroxymethyl-furfural (5-MHF) in an aqueous solution during autoclaving or steamed sterilization. Smith, et al. AM.J. Hosp. Pharm., 34:205–206 (1977). Because 5-HMF is considered to be harmful for the peritoneum (Henderson, et al., Blood Purif., 7:86–94 (1989)), it would be desirable to have a peritoneal dialysis solution with an osmotic agent as effective as glucose but which does not produce 5-HMF or other harmful decomposition products during autoclaving or sterilization. In short, a substitute osmotic agent for glucose is needed.
One family of compounds capable of serving as osmotic agents in peritoneal dialysis solutions is icodextrins, including maltodextrins. However, while these compounds are suitable for use as osmotic agents, they are also known to degrade during heat sterilization to aldonic acids and formaldehyde. Because the presence of formaldehyde in peritoneal dialysis solutions is inappropriate due to its poor biocompatibility, the use of icodextrins, including maltodextrins as a substitute for glucose as an osmotic agent is unsatisfactory.
Accordingly, there is a need for an improved peritoneal dialysis solution which utilizes an osmotic agent other than glucose and which is stable under autoclaving or steam sterilization conditions.